Method for treating symptoms of the onset of menopause using chromium

ABSTRACT

The method of this invention is directed to a treatment of alcohol craving in men and women and to a treatment of pre-menstrual syndrome (PMS) in women by administering to a patient a therapeutically effective amount of chromium in a pharmaceutically acceptable form either alone or in conjunction with the administration of a standard antidepressant composition, such as a selective serotonin reuptake inhibitor composition. Chromium is administered to the patient at dosages in a preferred range of about 200 to about 500 micrograms chromium.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a divisional of co-pending U.S. patentapplication Ser. No. 09/025,899 filed Feb. 19, 1998 herein incorporatedby reference, which is a divisional of co-pending U.S. patentapplication Ser. No. 08/901,841, filed Jul. 28, 1997, now U.S. Pat. No.5,877,171.

TECHNICAL FIELD

[0002] The present invention relates generally to a treatment foralcohol craving, a treatment for depression and to a treatment ofpre-menstrual syndrome, and more particularly to the treatment ofalcohol craving using chromium to the treatment of depression usingchromium and to the treatment of pre-menstrual syndrome using chromium.The present invention also particularly relates a method of improvingthe effectiveness of an antidepressant composition by administeringchromium to a patient concurrently with the administration of anantidepressant composition to the patient.

BACKGROUND ART

[0003] It will be appreciated by those having ordinary skill in the artthat depression is a difficult mental disorder to treat. Patients havingsuch a disorder are often reluctant to seek the medical attentionnecessary to diagnose the disorder. Such reluctance is often related tothe patient's fear of the stigma associated with seeking psychiatrichelp or to the patient's feelings of worthlessness associated withdepression. Moreover, once patients seek competent psychiatric help, itis difficult to successfully treat the disorder through psychoanalyticapproaches alone.

[0004] In the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition, (DSM IV) published by the American PsychiatricAssociation, depressive disorders are classified under mood disordersand are divided into three types: major depressive disorder, dysthymicdisorder and depressive disorder not otherwise specified. Majordepressive disorder and dysthymic disorder are differentiated based onchronicity, severity and persistence. In major depression the depressedmood must be present for two weeks. In dysthymic disorder the depressedmood must be present most days over a period of two (2) years. Usuallymajor depressive disorder is characterized by its sharp contrast tousual functioning. A person with a major depressive episode can befunctioning and feeling normally and suddenly develop severe symptoms ofdepression. By contrast a person with dysthymic disorder has chronicdepression with less severe symptoms than major depression.

[0005] In an effort to treat depression, a variety of antidepressantcompositions have been developed. Among these are the selectiveserotonin reuptake inhibitors (SSRI), such as sertraline (registeredtrademark ZOLOFT®—Pfizer), fluoxetine (registered trademark PROZAC®—EliLilly), paroxetine (trade name PAXIL™—Smith Kline Beecham) andfluvoxamine (trade name LUVOX™). Other examples of antidepressantcompositions include tricyclic antidepressants such as that sold underthe registered trademark ELAVIL® (Merck, Sharpe and Dohme), aminoketoneantidepressants such as bupropion, and lithium, a metal used to treatbipolar disorder. However, these drugs are very potent, often generatingproblematic side effects such as lethargy, clouded thinking and a lackof ability to concentrate.

[0006] Fluoxetine is also known to be efficacious in the treatment ofdysmenorrhea and pre-menstrual syndrome (PMS). Steiner et al., NewEngland Journal of Medicine 332:1529-34 (1995). The symptoms of PMSinclude dysphoria, craving for carbohydrates, exhaustion, muscle achesand cramps, among others. A detailed description of the symptoms of PMScan be found in the Diagnostic and Statistical Manual of MentalDisorders, Fourth Edition, (DSM IV) published by the AmericanPsychiatric Association. However, approximately forty percent (40%) ofwomen who are suffering from PMS do not have a positive response tofluoxetine when treated with it.

[0007] Chromium, in its pharmaceutically acceptable trivalent form, hasbeen used in the treatment of overeating as it is documented to controlappetite. Trivalent chromium is commercially available as chromiumpicolinate. Chromium has also been documented as playing a role infacilitating the action of insulin in the body. In this regard, toxicityconcerns relating to chromium have been demonstrated to be quite low.

[0008] There has been no description of the use of chromium in thetreatment of depression or in the treatment of pre-menstrual syndrome.

[0009] A method of treating neurological and mental disorders wasdescribed in Sandyk U.S. Pat. No. 5,470,846. However, the method of thisreference includes the application to the brain of a patient of asufficient amount of an AC pulsed magnetic field of proper intensity andfrequency to treat the disorder. In conjunction with the application ofthe AC pulsed magnetic field, a stimulant to facilitate the transport oftryptophan into the brain is administered. Chromium, preferably in theform of chromium picolinate, is described as a stimulant. However, whenthe disclosure of this application of chromium is taken as a whole, thedeficiencies become apparent. First of all, the application of the ACpulsed magnetic field is required in the method. Additionally, apatient, particularly in the case of depression, may be resistant toaccepting such a complex treatment.

[0010] Therefore, what is needed then is an effective,pharmacologically-based treatment for depression and for pre-menstrualsyndrome that potentiates the action and reduces the side effects ofknown compositions used in the treatment of these disorders. Such amethod of treatment is lacking in the prior art.

DISCLOSURE OF THE INVENTION

[0011] The method of this invention comprises the treatment ofdepression by administering to a patient a therapeutically effectiveamount of chromium in a pharmaceutically acceptable form either alone orin conjunction with the administration of a standard antidepressantcomposition. The administration of the pharmaceutically acceptable formof chromium does not need to be carried out in the presence of applyinga magnetic field to a patient and is desirably carried out in theabsence of any such application of a magnetic field.

[0012] Any standard antidepressant composition is contemplated to bewithin the scope of this invention. Among these are the selectiveserotonin reuptake inhibitors (SSRI), such as sertraline (registeredtrademark ZOLOFT®—Pfizer), fluoxetine (registered trademark PROZAC®—EliLilly), paroxetine (trade name PAXIL™—Smith Kline Beecham) andfluvoxamine (trade name LUVOX™). Other examples include tricyclicantidepressants such as that sold under the registered trademark ELAVIL®(Merck, Sharpe and Dohme), aminoketone antidepressants such asbupropion, and lithium, a metal used to treat bipolar disorder.

[0013] Chromium is administered one to three times a day. A preferredrange is about 50 to about 1,000 μg daily. A more preferred range isabout 100 to about 600 μg daily. A most preferred range is about 200 toabout 500 μg chromium daily. The preferred form of chromium is chromiumpicolinate.

[0014] Stated differently, a preferred range is about 1 μg to about 10μg chromium per kilogram body weight of the patient daily. A morepreferred range is about 2 μg to about 8 μg chromium per kilogram bodyweight of the patient daily. A most preferred range is about 4.5 μg toabout 6 μg chromium per kilogram body weight of the patient daily.

[0015] Also, contemplated to be within the scope of this invention are amethod of treating dysmenorrhea, a method of treating pre-menstrualsyndrome, a method of treating the symptoms of menopause and a method oftreating alcoholism. These methods comprise the administration of atherapeutically effective amount of chromium in a pharmaceuticallyacceptable form to a patient in need thereof. Similar dosage ranges asthose presented above are applicable to these methods.

[0016] Accordingly, it is an object of this invention to provide amethod of treating depression that is pharmacologically-based.

[0017] It is a further object of this invention to provide a method oftreating depression that is more appealing to patients.

[0018] It is yet a further object of this invention to provide a methodfor improving the effectiveness of anti-depressant compositions.

[0019] It is yet another object of this invention to provide a method oftreating alcoholism.

[0020] It is still another object of this invention to provide a methodof treating pre-menstrual syndrome (PMS).

[0021] Some of the objects of the invention having been statedhereinabove, other objects will become evident as the descriptionproceeds, when taken in connection with the accompanying drawings asbest described hereinbelow.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022]FIG. 1 is a graphical representation of the Beck Scale data fromPatient No. 1 in Example 1.

[0023]FIG. 2 is a graphical representation of SCL-90 Scale data fromPatient No. 1 in Example 1.

[0024]FIG. 3 is a graphical representation of the SCL-90 Subscale datafor Patient No. 1 in Example 1.

[0025]FIG. 4 is a graphical representation of the Beck Scale data forPatient No. 2 in Example 2.

[0026]FIG. 5 is a graphical representation of the SCL-90 Subscale datafrom Patient No. 2 in Example 2.

[0027]FIG. 6 is a graphical representation of the severity of thesymptoms of pre-menstrual syndrome as experienced by Patient No. 4 whentaking paroxetine and lithium.

[0028]FIG. 7 is a graphical representation of the severity of thesymptoms of pre-menstrual syndrome from Patient No. 4 in Example 4 whentaking no medication.

[0029]FIG. 8 is a graphical representation of the severity of thesymptoms of pre-menstrual syndrome when Patient No. 4 was takingparoxetine and chromium picolinate.

DETAILED DESCRIPTION OF THE INVENTION

[0030] As noted above, there are three types of depression generallycharacterized in the art, major depression, dysthymic disorder, ordysthymia, and depressive disorder not otherwise specified. Majordepression is characterized by peak episodes of extreme depression.During a peak episode, the patient may suffer from dysphoria, cravingfor carbohydrates, exhaustion, muscle aches, and dangerously suicidalnotions.

[0031] Dysthymia is characterized by chronic low moods that can last forlong periods of time in the life of the patient, such as 20 years.Dysthymia is further characterized by lack of passion for things in thesufferer's life, including work, food, and/or sexual relations, and bydysphoria.

[0032] As is recognized in the psychiatric art, depression may alsocomprise, and/or may also manifest itself in a variety of forms,including but not limited to, seasonal affective disorder, diurnal moodvariations, or depression associated with menopause. Diagnosis criteriafor dysthymia and major depression, as well as for seasonal affectivedisorder, diurnal mood variations and depression associated withmenopause, are more fully explained in the Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition, (DSM IV) published by theAmerican Psychiatric Association, the contents of which are hereinincorporated by reference.

[0033] Depression with seasonal affective pattern or seasonal affectivedisorder (hereinafter referred to as “SAD”) is also known as cabinfever, evening blues, and sun deprivation syndrome. The terms “seasonalaffective disorder” or “seasonal pattern specifier” are defined in theDSM-IV as a specifier or adjective that more precisely characterizesfeature associated with depression. A particular feature of SAD is theregular occurrence of depression in winter.

[0034] The term “diurnal mood variation” refers to rhythmical dailychanges in mood. It is described in the DSM-IV as a specifier(adjective) for depression, particular atypical depression. Theessential features of depression with diurnal mood variations(hereinafter referred to as “DMV”) are mood reactivity and the presenceof at least two of the following features: increased appetite or weightgain, hypersomnia, leaden paralysis (unexplained tiredness andexhaustion), and a long-standing pattern of extreme sensitivity toperceived interpersonal rejection. This type of depression is morecommon in women, and often, the first depressive episode occurs early inlife (e.g. in high school). This type of depression also tends to bechronic.

[0035] The method of this invention comprises the treatment ofdepression by administering to a patient a therapeutically effectiveamount of chromium in a pharmaceutically acceptable form either alone orin conjunction with the administration of a standard antidepressantcomposition. The administration of the pharmaceutically acceptable formof chromium does not need to be carried out in the presence of applyinga magnetic field to a patient and is desirably carried out in theabsence of any such application of a magnetic field.

[0036] In the methods of the instant invention, chromium is administeredone to three times a day. The preferred form of chromium, chromiumpicolinate, is commercially available. An acceptable source is marketedunder the trademark Nature Made®. From this source each tablet contains200 μg chromium from chromium picolinate. The tablets from this sourcealso include dibasic calcium phosphate, cellulose and magnesiumstearate. A daily nutritional value from chromium is yet to beestablished.

[0037] Thus, a preferred dosage range for chromium is about 50 to about1,000 μg daily. A more preferred range is about 100 to about 600 μgdaily. A most preferred range is about 200 to about 500 μg chromiumdaily. The preferred form of chromium is chromium picolinate.

[0038] Stated differently, a preferred range is about 1 μg to about 10μg chromium per kilogram body weight of the patient daily. A morepreferred range is about 2 μg to about 8 μg chromium per kilogram bodyweight of the patient daily.

[0039] Most preferred dosage ranges of chromium are those dosessufficient to deliver from about 4.5 to about 6 μg of chromium perkilogram (kg) of body weight. This dosage range is generally severalfold greater than that contained in most commercially availablemulti-vitamin and mineral preparations. This amount results in a plasmachromium level between 0.9 μg/liter to 2.1 μg/liter. The plasma levelwill vary depending on the level of exercise, i.e., the more oneexercises, the more chromium is required to maintain plasma levels.

[0040] To more fully characterize dosage information, the most preferreddosage range is calculated based on consuming enough chromium picolinateto deliver about 200 to about 500 μg elemental chromium. According tostandard stoichiometric calculations, in delivering 200 μg elementalchromium, approximately 1600 μg chromium picolinate is consumed in astandard commercial preparation.

[0041] It is also preferable to take the last, or only, daily dose ofchromium eight (8) hours prior to sleep to avoid insomnia. It is alsonoted that diabetics and hypoglycemics should use chromium only under aphysician's supervision.

[0042] Commercially available tubes for the collection of blood cancontain significant amounts of chromium. To avoid contamination, plasmalevels of chromium should be determined from blood collected inheparinized or EDTA tubes.

[0043] Also, contemplated to be within the scope of this invention are amethod of treating dysmenorrhea (painful menses), a method of treatingpre-menstrual syndrome (PMS), and a method of treating alcoholism oralcohol craving. It is particularly contemplated the dysmenorrhea and/orthe pre-menstrual syndrome to be treated comprise dysmenorrhea and/orpre-menstrual syndrome associated with menopause. Thus, it is anotheraspect of this invention to provide a method of treating the menopausalsymptoms of dysmenorrhea (painful menses), weight gain and depression.These methods comprise the administration of a therapeutically effectiveamount of chromium in a pharmaceutically acceptable form to a patient inneed thereof. In each method, chromium may be administered alone, or inconjunction with a standard antidepressant composition. Similar dosageranges as those presented above are applicable to these methods.

[0044] Any standard antidepressant composition is contemplated to bewithin the scope of this invention. Among these are the selectiveserotonin reuptake inhibitors (SSRI), such as sertraline (registeredtrademark ZOLOFT®—Pfizer), fluoxetine (registered trademark PROZAC®—EliLilly), paroxetine (trade name PAXIL™—Smith Kline Beecham) andfluvoxamine (trade name LUVOX™). Other examples include tricyclicantidepressants such as that sold under the registered trademark ELAVIL®(Merck, Sharpe and Dohme), aminoketone antidepressants such asbupropion, and lithium, a metal used to treat bipolar disorder.

[0045] In the foregoing examples, chromium picolinate is preferredsource of chromium. Other acceptable sources include chromium citrate,chromium chloride and chromium acetate. Other pharmaceuticallyacceptable forms of chromium would be apparent to one having ordinaryskill in the art.

[0046] The following examples are set forth to illustrate the subjectinvention. The examples should not be considered as limiting, the scopeof the invention being defined by the claims appended hereto.

EXAMPLE 1 Treatment of Dysthymia

[0047] Patient No. 1 was a 50-year old white male who, after a series ofpsychoanalysis/psychotherapy sessions, was diagnosed as suffering fromdepression in the form of dysthymia. Patient No. 1 experienced a chroniclow mood with markedly diminished interest and pleasure in allactivities including work, eating, and sexual relations.

[0048] Initially, Patient No. 1 was treated only with the knownantidepressant sertraline (sold under the registered trademark ZOLOFT®).Sertraline is a selective serotonin reuptake inhibitor. Sertraline wasadministered in amounts from 50 to 150 mg qd (per day); and it wasultimately determined that the ideal dose for this patient was 125 mg qd(per day). Sertraline provided some relief of the symptoms of dysthymia;but, often made the patient sluggish in his daily activities and madehis thinking cloudy, or fuzzy.

[0049] Independent of the sertraline treatments, the patient begantaking a vitamin and mineral supplement that included a series ofcomponents. While taking this vitamin and mineral supplement, thepatient noticed a marked improvement in his condition. As suchimprovement was unexpected, a study of the components of the mineralpreparation was undertaken. During this study Patient No. 1 stoppedtaking the composite preparation.

[0050] In this study, Patient No. 1 took one component of thepreparation at a time according to a schedule of one pill a day for fivedays, Monday through Friday. At the end of each week, he filled out twoself-rating scales that are used in the diagnosis and monitoring ofdepression. These scales are the Beck Scale and the SCL-90 Scale, bothof which are well known in the field of psychiatry and psychotherapy.Patient No. 1 continued to take sertraline at 125 mg per day. During thestudy, Patient No. 1 was not informed of what he was taking.

[0051] During the week prior to the beginning of the study, Patient No.1 took sertraline at 125 mg qd alone. He experienced loss of energy,disturbed sleep, and awaking tired. He also experienced a loss of musclestrength when exercising, muscle tightness in the neck and shoulders,hard bowel movements, frequent mild headaches, ringing in the ears(which has worsened since starting the sertraline), lack of focus on anyactivities, and loss of desire for sex. No Beck Scale or SCL-90 Scalewas given prior to this period.

[0052] During the first week of the study, Patient No. 1 received aplacebo of vitamin C along with the 125 mg of sertraline each day forfive days. His condition continued to worsen. His thought processes werecloudy, and he had trouble concentrating which interfered with his work.During a meeting at his work, he had trouble following the discussions.As demonstrated in the graph in FIG. 1, his total Beck score was +10,indicating a depressed condition.

[0053] During the second week, Patient No. 1 received chromium in theform of chromium picolinate. Patient No. 1 took 200 μg of chromium fromchromium picolinate per day along with 125 mg of sertraline. He noticeda dramatic, certain and immediate relief of symptoms. He observed anincrease in energy and his appetite was under control. His appearancewas relaxed and cheerful, as observed by the inventor in a meetingapproximately three days after Patient No. 1 began to take chromium. Thetotal Beck score at the end of the week was 0, indicating no depression.

[0054] During the third week, Patient No. 1 took 125 mg of sertralineqd. and one guarana pill each day. Guarana was selected as the nextcomponent because it contains caffeine. During this week, he becamedehydrated, had a slight headache and sore muscles, suffered fromdisturbed sleep and loss of energy, and his carbohydrate cravingreturned. He noted that he felt like he had taken too much caffeine. TheBeck score at the end of this week was a +2.

[0055] During the fourth week, Patient No. 1 took 125 mg sertraline qdand ginseng. Patient No. 1 observed that this week was better than lastweek, but not as good as the week before. He felt low on energy anddehydrated. At the end of this week, no chromium was detectable in hisplasma. His Beck score was also +1.

[0056] During the fifth week, Patient No. 1 took selenium and sertraline125 mg qd. During this week, he felt agitated, as when he had consumedtoo much caffeine. He also did not feel rested when he awoke from sleep.

[0057] At this point, the study was ceased. The patient inquired as towhat he wast taking during week 2 and was informed that he was takingchromium picolinate. On his own initiative, he consumed 400 μg ofchromium picolinate and immediately felt much better. Patient No. 1 thencontinued to take 400 μg of chromium of chromium picolinate per day (200μg twice daily or b.i.d.). Further, the patient discontinued thesertraline treatment to further characterize the relationship betweenchromium and sertraline. During this week, the patient noted that hissleep was much improved, that his mind was clearer than when he wastaking sertraline, that he did not crave food or alcohol, and that forthe first time in years he was hopeful about the future. At this pointin the study, his plasma chromium level was 0.9 μg/L.

[0058] For Patient No. 1, a potential adverse side effect was observed.The patient reported that after taking 200 μg of chromium from chromiumpicolinate late in the day, his sleep was disturbed. He thereforedecided to take it no later than 3:00 p.m. He then reported that heslept much better after taking the second dose of chromium picolinateearlier in the day.

[0059] The patient's progress was tracked over an additional six-weekperiod. The patient stated that he had felt the best he had felt in adecade. He characterized himself as feeling good mentally andphysically. He stated that he began to feel normal. He felt better whentaking the chromium picolinate alone than when taking chromiumpicolinate and sertraline at the same time. The patient stated that hefelt a “a bit slowed down” and his thinking was dulled when he takingsertraline in addition to the chromium picolinate.

[0060] Patient No. 1 further observed that during a crisis period atwork during the last week of the study described herein, he increasedhis chromium from chromium picolinate intake to 200 μg t.i.d., or threetimes daily. Within an hour, he noticed immediate improvement and wasable to deal with his crisis.

[0061] The series of events described in the above example are morefully set forth in the graphs in FIGS. 1 and 2. FIG. 1 is a bar graphdisplaying the scores on the Beck Scale, a self-rating scale fordepression, at the end of each weekly treatment.

[0062]FIG. 2 is a bar graph of the total score on the SCL-90 Scale. TheSCL-90 is composed of 90 questions. It is designed to measure symptomsof somatization, obsessive-compulsive behavior, interpersonalsensitivity, depression, anxiety, hostility, phobic anxiety, paranoidideation, and psychoticism. It is noted that the grand total of scoreson each Friday closely parallels the results of the Beck Scale.

[0063]FIG. 3 is a graph of three subscales of the SCL-90 (somatization,obsessive-compulsive, and depression). These subscales reflect thegreatest changes. The marked elevation on the somatization scale duringthe week after chromium picolinate was stopped may have been due to thecaffeine effect of guarana and/or lack of chromium picolinate. It isnoted that the positive reading during the last week of the therapy wasdue to Patient No. 1 experiencing certain unpleasant and unwantedthoughts regarding the crisis at his work referenced above. There was noreturn of somatic symptoms of depression.

Treatment of Alcoholism or Alcohol Craving

[0064] During the later stages of the study described above, whenPatient No. 1 was taking chromium picolinate alone, he also noticed achange in his ability to tolerate alcohol. Both of his parents werealcoholics so he guarded carefully against this outcome by drinkinginfrequently.

[0065] Despite this effort, he often experienced intense cravings foralcohol. Prior to his treatment with chromium, when he consumed alcohol,he could only drink it by gulping it. He experienced rapid intoxication,unpleasant feelings, and a severe hangover the next day. Since treatmentwith chromium picolinate began as described above, he observedsignificantly diminished alcohol cravings. He also observed that hecould drink in moderation, without having a severe hangover the nextday.

[0066] Thus, a method of treating alcoholism or alcohol cravings iscontemplated to be within the scope of this invention.

EXAMPLE 2 Treatment of Dysthymia

[0067] Patient No. 2 was a 25-year old single white female. She is thedaughter of Patient No. 1. She complained of weight gain, hyperphagia,hypersomnia, loss of interest in sex, irritability and an inability toconcentrate. She stated that she had been seeing psychotherapists sinceshe was 13 years old, but had no success in dealing with her depression.She was also diagnosed as having dysthymia.

[0068] She had taken sertraline in the amount of 50 mg qd. with littlehelp. This dosage was increased to 100 mg qd. which proceeded for aperiod of five weeks. She was still symptomatic of depression, but feltbetter. She was not as weepy and her outlook was less negative. Herinterest in sex was increased. Her appetite remained the same. Thesertraline treatment improved her interest in a former hobby, reading.

[0069] Patient No. 2 then began a similar study as that described abovefor Patient No. 1. For the first week, she took one vitamin C tabletdaily along with 100 mg of sertraline. Her depression appeared to worsenas reflected by her grand total Beck score of +12 and her SCL-90 +4 asmore fully portrayed on the FIG. 5. She suggested that it was moredifficult to more accurately evaluate women because of PMS.

[0070] During the second week, Patient No. 2 started 200 μg of chromiumfrom chromium picolinate per day and continued 100 mg sertraline perday. Her SCL-90 score demonstrated a definite improvement. She wrote onher Beck Scale that her appetite was less.

[0071] For week three she took guarana and continued sertraline at 100mg per day. She noted that she did not feel as well during this week asthe previous week. Week three was also the start of her menstrual cyclein which she normally experienced PMS.

[0072] During the fourth week she took ginseng and continued sertralineat 100 mg per day. During the middle of this week she complained of lowenergy, headache, restlessness, and initial insomnia. She stated thatshe definitely had less energy than week two when she was takingchromium picolinate.

[0073] During week five she began taking St. John's Wort, a herbbelieved to have antidepressant effects. She also continued sertralineat 100 mg per day. No positive response was observed.

[0074] During week six she began taking selenium and continued 100 mgsertraline per day. Her food craving returned and she generally did notfeel well. At this point, Patient No. 2 became impatient with this studyand wished to resume taking the medication that was effective. Shetherefore discontinued taking selenium and began taking chromiumpicolinate at 200 μg per day beginning the Monday of the next week.

[0075] Within two days she felt better and had no symptoms. Sheconsidered the study over and therefore did not take either the BeckScale of the SCL-90. It was estimated via a telephone interview that herBeck Scale was +2. Four days following her resuming treatment withchromium picolinate her plasma chromium was 0.8 μg/L.

[0076] Patient No. 2 continued to take sertraline along with chromiumpicolinate because of a stressful situation at her workplace. Despitethis added stress at work, she noted that she was able to function muchbetter than in the past. She stated that things just did not seem tobother her as much as they used to bother her.

Treatment of Pre-Menstrual Syndrome (PMS)

[0077] While Patient No. 2 was taking chromium picolinate according tothe dosages described above, she further observed that her menses wasless problematic. She said that she had less carbohydrate craving duringthe week before, that she was less irritable, that her dysphoria wasrelieved, and that her usual cramps were non-existent. Thus, an aspectof the present invention includes the treatment of pre-menstrualsyndrome (PMS), or dysmenorrhea (problematic and/or painful menses),comprising administering chromium in a preferred dose of 200 μg per dayto a patient in need thereof.

[0078] For Patient No. 2, FIG. 5 presents Patient No. 2's Beck Scaletotal scores, and FIG. 6 presents a graph of the four subscales ofsomatization, obsessive-compulsive, depression, anxiety on the SCL-90Scale.

EXAMPLE 3 Treatment of Severe Dysthymia

[0079] Patient No. 3 was a 42-year old divorced man experiencing chronicsuicidal depression for about 15 years. For as long as the patient canremember, he has had episodic, mild-to-moderate mood swings.Approximately 15 years ago his condition worsened and he was depressedalmost daily. His thoughts were slowed down, he felt intensely sad,guilty, worthless, confused, and desperate. Over a period ofapproximately two years he underwent therapy with a social worker andpsychotherapy with a psychiatrist, with little positive results. Nopharmaco-therapy was involved in either of these treatments.

[0080] Initially, Patient No. 3 met with the inventor and identified achildhood source as a partial cause of his depression, low self-esteemand dysfunctional thinking. Although he appreciated the insights gainedthrough the psychoanalysis/psychotherapy with the inventor, hisdepression persisted unabated. He was rejected by his girlfriend andbecame frighteningly suicidal.

[0081] Approximately eight months prior to the beginning of thetreatment as described below, he began taking 50 mg of ELAVIL® (aregistered trademark for Merck, Sharpe and Dohme for the antidepressant,amitryptline HCl, a tricyclic antidepressant) per day which helped himsleep and allowed him, in his words, to think more rationally. Withinsix months he developed a tolerance to the drug and it was increased to100 mg per day with no effect. He stopped ELAVIL® and started bupropion100 mg b.i.d and lithium 300 mg t.i.d. Bupropion is an aminoketoneantidepressant, and lithium is a metal used to treat bipolar disorder.

[0082] The bupropion treatment was discontinued because he developedinvoluntary muscle twitches. His condition was desperate andlife-threatening. He was therefore prescribed sertraline at 100 mg qdand was given 12 200 μg pills of chromium picolinate with instructionsto take one pill b.i.d., or twice daily.

[0083] Patient No. 3 observed that after four to five days there was aperceptible change in his mood. He stated that he felt close tocontentment and might be there soon.

[0084] Thus, another aspect of this invention is that administration ofchromium in conjunction with the administration of a selective serotoninreuptake inhibitor (SSRI) like sertraline reduces the delay in the lagtime normally associated with an SSRI. Stated differently, there is lagtime of normally 30 days before the SSRI's effect on depression isnoted. In this case, Patient No. 3 experienced relief of symptoms withinfour to five days.

[0085] Two to three days after he took the last chromium picolinatetablets he began to feel as if he were slipping back and began feelingsad and pessimistic. He was then given a three-week supply of chromiumpicolinate so that he could take one pill providing 200 μg of chromiumfrom chromium picolinate twice daily. Within a matter of days, PatientNo. 3 noted that he rebounded and felt better than he had felt in manyyears.

[0086] He further observed that he felt like himself again and that hefelt content in many ways. He stated that he had gained control of hislife that he had felt deprived of for so long. He noted that instead ofobsessing for many hours over his low mood and past mistakes, he wasable to focus on practical matters. He became optimistic about hisfuture and about his artistic endeavors. He also felt as if his mind wasbecoming unburdened of much of the negative clutter that kept him fromdealing with his problems.

[0087] While taking chromium picolinate, Patient No. 3 was againrejected by his girlfriend. Rather than slipping again into depression,he accepted this in stride and continued with his life.

[0088] Therefore, Patient No. 3, a patient suffering from severedysthymia, noticed marked improvement after taking chromium picolinatein a preferred dosage providing chromium in the amount of 200 μg twicedaily, or 400 μg per day.

EXAMPLE 4 Treatment of Major Depression, Dysphoria and Pre-MenstrualSyndrome

[0089] Patient No. 4 was a 45-year old woman who has struggled toovercome a wide variety of psychiatric symptoms, two of which aredepression and pre-menstrual syndrome (PMS). After several treatments,it was determined that a combination of paroxetine 20 mg t.i.d. andlithium 300 mg t.i.d. diminished her symptoms of obsessive-compulsivedisorder, depression, hypomania and PMS. While taking this combination,she rated her PMS as moderate to severe and barely tolerable. See thechart more fully set forth in FIG. 6.

[0090] In FIGS. 6-8 the abbreviations for each symptom on the graphs maybe translated as follows:

[0091] dep=depression

[0092] anx=anxiety

[0093] lab mood=mood swings

[0094] ang=anger

[0095] dec int=decreased interest in activities

[0096] con=difficulty in concentrating

[0097] en=lack of energy, fatigue

[0098] fd=food cravings

[0099] slp=sleep disturbance

[0100] con=loss of control

[0101] phy=physical symptoms (i.e., breast swelling)

[0102] impair=impaired in work, school, relationships

[0103] Patient No. 4's formal diagnoses were multiple personalitydisorder, obsessive-compulsive disorder, major depression disorder,alcoholism (recovering), and pre-menstrual syndrome (PMS).

[0104] Set forth below in Table 1 are the research criteria set forth inthe Diagnostic and Statistical Manual of Mental Disorders, Forthedition, published by the American Psychiatric Association forPre-Menstrual Dysphoric Disorder, or Pre-Menstrual Syndrome.

TABLE 1 Research Criteria for Pre-Menstrual Dysphoric Disorder

[0105] A. In most menstrual cycles during the past year, five (or more)of the following symptoms were present for most of the time during thelast week of the luteal phase, began to remit within a few days afterthe onset of the follicular phase, and were absent in the weekpostmenses, with at least one of the symptoms being either (1), (2), (3)or (4):

[0106] (1) markedly depressed mood, feelings of hopelessness, orself-deprecating thoughts;

[0107] (2) marked anxiety, tension, feelings of being “keyed up,” or “onedge”;

[0108] (3) marked affective lability (e.g., feeling suddenly sad ortearful or increased sensitivity to rejection);

[0109] (4) persistent and marked anger or irritability or increasedinterpersonal conflicts;

[0110] (5) decreased interest in usual activities (e.g., work, school,friends, hobbies);

[0111] (6) subjective sense of difficulty in concentrating;

[0112] (7) lethargy, easy fatigability, or marked lack of energy;

[0113] (8) marked change in appetite, overeating, or specific foodcravings;

[0114] (9) hypersomnia or insomnia;

[0115] (10) a subjective sense of being overwhelmed or out of control;

[0116] (11) other physical symptoms, such as breast tenderness orswelling, headaches, joint or muscle pain, a sensation of “bloating,”weight gain.

[0117] Note: In menstruating females, the luteal phase corresponds tothe period between ovulation and the onset of menses, and the follicularphase begins with menses. In non-menstruating females (e.g., those whohave had a hysterectomy), the timing of luteal and follicular phases mayrequire measurement of circulating reproductive hormones.

[0118] B. The disturbance markedly interferes with work or school orwith usual social activities and relationships with others (e.g.,avoidance of social activities, decreased productivity and decreasedefficiency at work or school.)

[0119] C. The disturbance is not merely an exacerbation of the symptomsof another disorder, such as Major Depressive Disorder, Panic Disorder,Dysthymic Disorder, or a Personality Disorder (although it may besuperimposed on any of these disorders.)

[0120] D. Criteria A, B and C must be confirmed by prospective dailyratings during at least two consecutive symptomatic cycles. (Thediagnosis may be made provisionally prior to this confirmation).

[0121] Patient No. 4 had a history of severe PMS that started when shewas 30 years old. She described a typical menses as follows. She wasusually moderately to severely depressed for at least two days duringthe week before her menses. She had sudden mood swings. One moment shewould be crying and the next she would be laughing wildly, or she wouldhave sudden outbursts of anger. She was markedly tense and would fidgetconstantly. She tired easily and lacked energy. She could barely dragherself out of bed each morning. She craved carbohydrates and oftenwould eat several doughnuts, whole cakes, or boxes of cookies. She sleptlittle, and for two or three nights she would have night sweats thatdrenched her bed. She also experienced back cramps, bloating and painsin her joints and muscles. She had trouble concentrating and was unableto do life's simplest chores. Her PMS interfered with her ability tofunction. She lost interest in her favorite hobby, reading.

[0122] She was prescribed paroxetine because of its documented efficacyin the treatment of obsessive-compulsive disorder. Patient No. 4 alsonoticed that it reduced the severity of her symptoms of PMS from severeto moderately severe. The chart in FIG. 6 depicts patient No. 4's ratingof her late luteal phase symptoms during a month. During this month, shewas taking paroxetine 20 mg t.i.d. and 300 mg of lithium t.i.d. Shedescribed this as typical of the menstrual cycles she has while takingparoxetine. Paroxetine decreased the severity of her symptoms but didnot eliminate them. It had little to no effect on her energy level,carbohydrate craving and other physical symptoms.

[0123] Due to a gastrointestinal disturbance that lasted approximatelysix weeks, patient No. 4 was unable to take the paroxetine and lithiumcombination as described above for approximately three weeks. Her“black” depression returned and she frequently thought of suicide. Whileoff paroxetine and lithium, her PMS was severe. It reminded her of themenses she had experienced before she started paroxetine. FIG. 7 depictspatient No. 4's rating of her symptoms of pre-menstrual symptoms duringthe late luteal phase of her menstrual cycle wherein she had not takenany of the medication in three weeks. This depicts that this menses wasone of the more severe ones that she had experienced and was typical ofher menses before taking paroxetine.

[0124] After her gastrointestinal symptoms subsided, she was left weak,frail, dizzy, depressed and crippled by hand-washing and other ritualsthat characterized her obsessive-compulsive disorder. She resumedlithium 300 mg t.i.d. and paroxetine 40 mg per day, but her depressionwas refractory. The inventor then suggested that she begin takingchromium picolinate. At the time of the suggestion, her plasma containedno detectable chromium.

[0125] About a week later, she started taking chromium picolinate at adosage providing 200 μg of chromium twice a day. She started takingchromium picolinate in this amount on the fourth day of menstruation.Thus, she would expect her pre-menstrual syndrome to begin approximatelytwo weeks after beginning to take chromium picolinate.

[0126] However, she was not aware of any of the symptoms ofpre-menstrual syndrome (except for breast swelling). She was surprisedat the onset of menses. For the first time in her recent memory, she wascompletely without signs or symptoms of PMS, except for breast swelling.Though she experienced breast swelling, she did not experience breasttenderness. The chart presented in FIG. 8 depicts patient No. 4's ratingof her symptoms of PMS while taking paroxetine 20 mg t.i.d., lithium 300mg t.i.d., and chromium picolinate providing 200 μg of chromium b.i.d.Her only symptoms were a slight sleep disturbance and breast swelling.Patient No. 4 noted that this was the least troublesome menses that shehad experienced in 15 years.

[0127] Thus, an aspect of the present invention includes the treatmentof pre-menstrual syndrome (PMS) comprising administering chromium in apreferred dose of 200 μg b.i.d. to a patient in need thereof.Additionally, as paroxetine is a selective serotonin reuptake inhibitorand an antidepressant, it is an aspect of this invention to improve theeffectiveness in administering such a composition for the treatment ofpre-menstrual syndrome. Therefore, the present invention relates to atreatment of depression in men and women and to a treatment ofpre-menstrual syndrome (PMS) in women using chromium, in a preferredform of chromium picolinate, alone or in conjunction with anantidepressant composition, such as a selective serotonin reuptakeinhibitor (SSRI). Chromium potentiates the action of SSRI's and relievesthe dysphoria in depression and PMS, reduces or eliminates othersymptoms of depression (including craving for carbohydrates, exhaustionand muscle aches), reduces the lag time between administration of SSRI'sand clinical response, and reduces the side effects of SSRI's. Further,chromium is neurobiologically active and acts independently of theantidepressant composition, such as an SSRI.

[0128] It will be understood that various details of the invention maybe changed without departing from the scope of the invention.Furthermore, the foregoing description is for the purpose ofillustration only, and not for the purpose of limitation—the inventionbeing defined by the claims.

What is claimed is:
 1. A method of treating alcohol craving in apatient, the method comprising the steps of (a) administering atherapeutically effective amount of chromium in a pharmaceuticallyacceptable form to a patient in need thereof; and (b) relieving alcoholcraving in the patient by said administering of said therapeuticallyeffective amount of chromium.
 2. The method according to claim 1 whereinchromium is administered in a dose ranging from about 50 μg to about1,000 μg daily.
 3. The method according to claim 2 wherein chromium isadministered in a dose ranging from about 100 μg to about 600 μg daily.4. The method according to claim 3 wherein chromium is administered in adose ranging from about 200 μg to about 500 μg daily.
 5. The methodaccording to claim 1 wherein the therapeutically effect amount isadministered at least once a day.
 6. The method according to claim 1wherein the therapeutically effect amount is administered at least twicea day.
 7. The method according to claim 1 wherein the therapeuticallyeffect amount is administered three times a day.
 8. The method accordingto claim 1 wherein chromium is administered in a dose ranging from about1 μg to about 10 μg per kilogram body weight of the patient daily. 9.The method according to claim 8 wherein chromium is administered in adose ranging from about 2 μg to about 8 μg per kilogram body weight ofthe patient daily.
 10. The method according to claim 9 wherein chromiumis administered in a dose ranging from about 4.5 μg to about 6 μg perkilogram body weight of the patient daily.
 11. A method of treatingalcohol craving in a patient, the method comprising the steps of (a)administering a therapeutically effective amount of chromium in apharmaceutically acceptable form to a patient in need thereof, saidtreating of alcohol craving being free of administering to the patientother compositions to treat alcohol craving; and (b) relieving alcoholcraving in the patient by said administering of said therapeuticallyeffective amount of chromium.
 12. The method according to claim 11wherein chromium is administered in a dose ranging from about 50 μg toabout 1,000 μg daily.
 13. The method according to claim 12 whereinchromium is administered in a dose ranging from about 100 μg to about600 μg daily.
 14. The method according to claim 13 wherein chromium isadministered in a dose ranging from about 200 μg to about 500 μg daily.15. The method according to claim 11 wherein the therapeutically effectamount is administered at least once a day.
 16. The method according toclaim 11 wherein the therapeutically effect amount is administered atleast twice a day.
 17. The method according to claim 11 wherein thetherapeutically effect amount is administered three times a day.
 18. Themethod according to claim 11 wherein chromium is administered in a doseranging from about 1 μg to about 10 μg per kilogram body weight of thepatient daily.
 19. The method according to claim 18 wherein chromium isadministered in a dose ranging from about 2 μg to about 8 μg perkilogram body weight of the patient daily.
 20. The method according toclaim 19 wherein chromium is administered in a dose ranging from about4.5 μg to about 6 μg per kilogram body weight of the patient daily.